Our long-term goal is to continue characterization of some of the patterns and mechanisms of inflammatory reactions in human allergic reactions and asthma. Through use of skin chambers and microscopic studies of biopsies we will 1) compare early mast cell changes with subsequent in vivo mediator release, inflammatory cell infiltration, possible local coagulation activation, and enzymatic responses; 2) study the relationship of these events to late phase skin reactions to antigen; 3) study in vivo effects of products released into the chamber during allergic reactions; 4) investigate possible modulation by therapeutic agents and "feed back" inhibition by histamine. In the same subjects, changes in mediator levels and leukocytes in the blood will be studied during antigen inhalation induced bronchoconstriction in both early and late phases, and the modulation by therapy. We will further characterize the physio-chemical and biological properties of the serum neutrophil chemotactic activity which we found during such asthmatic reactions. In these ways we will learn more about in vivo events during skin and respiratory human allergic reactions, the effects in the responding cells, the role of coagulation/kinin activation and the role of such events in immediate and late responses to antigen.